MiR-155/GSK-3β mediates anti-inflammatory effect of Chikusetsusaponin IVa by inhibiting NF-κB signaling pathway in LPS-induced RAW264.7 cell

Abstract It has been demonstrated that Chikusetsusaponin IVa (CsIVa) possesses abundant biological activities. Herein, using LPS to establish acute inflammation model of mouse liver and cell line inflammation model, we investigated whether miR-155/GSK-3β regulated NF-κB signaling pathway, and CsIVa exerted anti-inflammatory effects by regulating miR-155/GSK-3β signaling pathway. Our results showed that LPS induced high expression of miR-155 and miR-155 promoted macrophage activation through GSK-3β. In addition, CsIVa inhibited inflammatory responses in LPS-induced mouse liver and RAW264.7 cells. Furthermore, we demonstrated that CsIVa improved the inflammatory response in LPS-induced RAW264.7 cells by inhibiting miR-155, increasing GSK-3β expression, and inhibiting NF-κB signaling pathway. In conclusion, our study reveals that CsIVa suppresses LPS-triggered immune response by miR-155/GSK-3β-NF-κB signaling pathway.

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Ethanol Extract of Lilium Bulbs Plays an Anti-Inflammatory Role by Targeting the IKKα/β-Mediated NF-κB Pathway in Macrophages

The American Journal of Chinese Medicine ◽

10.1142/s0192415x18500672 ◽

2018 ◽

Vol 46 (06) ◽

pp. 1281-1296 ◽

Cited By ~ 9

Author(s):

Sang Yun Han ◽

Young-Su Yi ◽

Seong-Gu Jeong ◽

Yo Han Hong ◽

Kang Jun Choi ◽

...

Keyword(s):

Nitric Oxide ◽

Signaling Pathway ◽

Nuclear Translocation ◽

Inflammatory Responses ◽

Inflammatory Activity ◽

Raw264.7 Cells ◽

No Production ◽

Dependent Manner ◽

Bioactive Components ◽

Anti Inflammatory

Lilium bulbs have long been used as Chinese traditional medicines to alleviate the symptoms of various human inflammatory diseases. However, mechanisms of Lilium bulb-mediated anti-inflammatory activity and the bioactive components in Lilium bulbs remain unknown. In the present study, the anti-inflammatory activity of Lilium bulbs and the underlying mechanism of action were investigated in macrophages using Lilium bulb ethanol extracts (Lb-EE). In a dose-dependent manner, Lb-EE inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and bone marrow-derived macrophages (BMDMs) without causing significant cytotoxicity. Lb-EE also down-regulated mRNA expression of inflammatory genes in LPS-stimulated RAW264.7 cells, which included inducuble nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]). Furthermore, Lb-EE markedly restored LPS-induced morphological changes in RAW264.7 cells to a normal morphology. HPLC analysis identified quercetin, luteolin, and kaempferol as bioactive components contained in Lb-EE. Mechanistic studies in LPS-stimulated RAW264.7 cells revealed that Lb-EE suppressed MyD88- and TRIF-induced NF-[Formula: see text]B transcriptional activation and the nuclear translocation of NF-[Formula: see text]B transcription factors. Moreover, Lb-EE inhibited IKK[Formula: see text]/[Formula: see text]-induced activation of the NF-[Formula: see text]B signaling pathway and IKK inhibition significantly reduced NO production in LPS-stimulated RAW264.7 cells. Taken together, these results suggest that Lb-EE plays an anti-inflammatory role by targeting IKK[Formula: see text]/[Formula: see text]-mediated activation of the NF-[Formula: see text]B signaling pathway during macrophage-mediated inflammatory responses.

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Sodium Fluoride (NaF) Induces Inflammatory Responses Via Activating MAPKs/NF-κB Signaling Pathway and Reducing Anti-inflammatory Cytokine Expression in the Mouse Liver

Biological Trace Element Research ◽

10.1007/s12011-018-1458-z ◽

2018 ◽

Vol 189 (1) ◽

pp. 157-171 ◽

Cited By ~ 8

Author(s):

Linlin Chen ◽

Ping Kuang ◽

Huan Liu ◽

Qin Wei ◽

Hengmin Cui ◽

...

Keyword(s):

Signaling Pathway ◽

Sodium Fluoride ◽

Mouse Liver ◽

Inflammatory Cytokine ◽

Inflammatory Responses ◽

Cytokine Expression ◽

Anti Inflammatory ◽

Anti Inflammatory Cytokine

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Anti-Inflammatory Effects of Berchemia floribunda in LPS-Stimulated RAW264.7 Cells through Regulation of NF-κB and MAPKs Signaling Pathway

Plants ◽

10.3390/plants10030586 ◽

2021 ◽

Vol 10 (3) ◽

pp. 586

Author(s):

Hyun Ji Eo ◽

Jun Hyuk Jang ◽

Gwang Hun Park

Keyword(s):

Signaling Pathway ◽

Inflammatory Activity ◽

Nuclear Accumulation ◽

Raw264.7 Cells ◽

No Production ◽

Tnf Α ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Inflammatory Effect

Berchemia floribunda (Wall.) Brongn. (BF), which belongs to Rhamnaceae, is a special plant of Anmyeon Island in Korea. BF has been reported to have antioxidant and whitening effects. However, the anti-inflammatory activity of BR has not been elucidated. In this study, we evaluated the anti-inflammatory effect of leaves (BR-L), branches (BR-B) and fruit (BR-F) extracted with 70% ethanol of BR and elucidated the potential signaling pathway in LPS-induced RAW264.7 cells. BR-L showed a strong anti-inflammatory activity through the inhibition of NO production. BR-L significantly suppressed the production of the pro-inflammatory mediators such as iNOS, COX-2, IL-1β, IL-6 and TNF-α in LPS-stimulated RAW264.7 cells. BR-L suppressed the degradation and phosphorylation of IκB-α, which contributed to the inhibition of p65 nuclear accumulation and NF-κB activation. BR-L obstructed the phosphorylation of MAPKs (ERK1/2, p38 and JNK) in LPS-stimulated RAW264.7 cells. Consequently, these results suggest that BR-L may have great potential for the development of anti-inflammatory drugs to treat acute and chronic inflammatory disorders.

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Anti-Inflammatory Effect of Piper attenuatum Methanol Extract in LPS-Stimulated Inflammatory Responses

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/4606459 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

You Jin Kim ◽

Jeong Deok ◽

Sunggyu Kim ◽

Deok Hyo Yoon ◽

Gi-Ho Sung ◽

...

Keyword(s):

Signaling Pathway ◽

Intracellular Signaling ◽

Methanol Extract ◽

Inflammatory Responses ◽

Mechanisms Of Action ◽

No Synthase ◽

Poly I:C ◽

Prostaglandin E ◽

Anti Inflammatory ◽

Inflammatory Effect

Piper attenuatum is used as a traditional medicinal plant in India. One of the substances in P. attenuatum has been suggested to have anti-inflammatory effects. However, there is insufficient research about the anti-inflammatory mechanisms of action of P. attenuatum. The effects of P. attenuatum methanol extract (Pa-ME) on the production of inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2), the expression of proinflammatory genes, the translocation level of transcription factors, and intracellular signaling activities were investigated using macrophages. Pa-ME suppressed the production of NO and PGE2 in lipopolysaccharide- (LPS-), pam3CSK4-, and poly(I:C)-stimulated RAW264.7 cells without displaying cytotoxicity. The mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2) were decreased by Pa-ME. P-ME reduced the translocation of p50/NF-κB and AP-1 (c-Jun and c-Fos), as well as the activity of their upstream enzymes Src, Syk, and TAK1. Immunoprecipitation analysis showed failure of binding between their substrates, phospho- (p-) p85 and p-MKK3/6. p-p85 and p-MKK3/6, which were induced by overexpression of Src, Syk, and TAK1, were also reduced by Pa-ME. Therefore, these results suggest that Pa-ME exerts its anti-inflammatory effects by targeting Src and Syk in the NF-κB signaling pathway and TAK1 in the AP-1 signaling pathway.

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Anti-inflammatory effect of a novel formulation of coconut inflorescence sap against ox-LDL induced inflammatory responses in human peripheral blood mononuclear cells by modulating TLR-NF-κB signaling pathway

Toxicology Mechanisms and Methods ◽

10.1080/15376516.2017.1344339 ◽

2017 ◽

Vol 27 (8) ◽

pp. 615-621 ◽

Cited By ~ 5

Author(s):

M. Ratheesh ◽

Jose P. Svenia ◽

S. Asha ◽

S. Sandya ◽

B. Girishkumar ◽

...

Keyword(s):

Signaling Pathway ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Inflammatory Responses ◽

Human Peripheral Blood ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Anti Inflammatory ◽

Inflammatory Effect

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Atraric Acid Exhibits Anti-Inflammatory Effect in Lipopolysaccharide-Stimulated RAW264.7 Cells and Mouse Models

International Journal of Molecular Sciences ◽

10.3390/ijms21197070 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7070

Author(s):

Seul-Ki Mun ◽

Kyung-Yun Kang ◽

Ho-Yeol Jang ◽

Yun-Ho Hwang ◽

Seong-Gyeol Hong ◽

...

Keyword(s):

Nitric Oxide ◽

Signaling Pathway ◽

Inflammatory Diseases ◽

Treated Group ◽

Endotoxin Shock ◽

Raw264.7 Cells ◽

Symbiotic Association ◽

Extracellular Signal ◽

Anti Inflammatory ◽

Inflammatory Effect

Lichens, composite organisms resulting from the symbiotic association between the fungi and algae, produce a variety of secondary metabolites that exhibit pharmacological activities. This study aimed to investigate the anti-inflammatory activities of the secondary metabolite atraric acid produced by Heterodermia hypoleuca. The results confirmed that atraric acid could regulate induced pro-inflammatory cytokine, nitric oxide, prostaglandin E2, induced nitric oxide synthase and cyclooxygenase-2 enzyme expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Meanwhile, atraric acid downregulated the expression of phosphorylated IκB, extracellular signal-regulated kinases (ERK) and nuclear factor kappa B (NFκB) signaling pathway to exhibit anti-inflammatory effects in LPS-stimulated RAW264.7 cells. Based on these results, the anti-inflammatory effect of atraric acid during LPS-induced endotoxin shock in a mouse model was confirmed. In the atraric acid treated-group, cytokine production was decreased in the peritoneum and serum, and each organ damaged by LPS-stimulation was recovered. These results indicate that atraric acid has an anti-inflammatory effect, which may be the underlying molecular mechanism involved in the inactivation of the ERK/NFκB signaling pathway, demonstrating its potential therapeutic value for treating inflammatory diseases.

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Facile Synthesis, Characterization and Anti-Inflammatory Effect of 3-Aminoindolizine Derivatives

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.881-883.446 ◽

2014 ◽

Vol 881-883 ◽

pp. 446-449

Author(s):

Yong Wei ◽

Cheng Qiao Cao ◽

Xiao Feng Lu ◽

Zheng Yang ◽

Kun Zou ◽

...

Keyword(s):

Elemental Analysis ◽

Biological Activities ◽

Bacterial Lipopolysaccharide ◽

Facile Synthesis ◽

Inflammation Model ◽

Mouse Cells ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Stimulation Of ◽

Inflammatory Effect

Four 3-aminoindolizines were synthesized from the substituted 2-bromopyridines and propargyl amines with the aim of obtaining potential anti-inflammatory compounds, which were characterized by NMR, IR, ESI-MS and elemental analysis. Their biological activities were evaluated by the bacterial lipopolysaccharide (LPS) stimulation of mouse cells in the RAW264.7 inflammation model. The target compounds4a-4drevealed moderate anti-inflammatory effects with the inhibitions of 45%~61% at 50 μM. The bioactive 3-aminoindolizines might be used for further optimization as potential anti-inflammatory drugs.

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Inhibition of chikusetsusaponin IVa on inflammatory responses in RAW264.7 cell line via MAPK pathway

Zeitschrift für Naturforschung C ◽

10.1515/znc-2019-0107 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Guangren Xu ◽

Hongyu Lei ◽

Qiaoling Yuan ◽

Huiyu Chen ◽

Jianming Su

Keyword(s):

Nitric Oxide ◽

Inflammatory Responses ◽

Mapk Pathway ◽

Biological Activities ◽

Interleukin 10 ◽

Raw264.7 Cell ◽

Anti Inflammatory ◽

Underlying Mechanisms ◽

Factor Α ◽

Oxide Synthase

AbstractChikusetsusaponin IVa (CHS-IVa), a saponin from herb Panacis japonicas, possesses extensive biological activities. However, the roles and underlying mechanisms of CHS-IVa on inflammation have not been fully clarified in the setting of murine macrophages. In this study, we found that CHS-IVa effectively reduced the expression of inflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-1β (IL-1β), cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells. Meanwhile, CHS-IVa could also evidently bate the contents of nitric oxide (NO) and prostaglandin E2 (PGE2) in cell culture supernatants. Furthermore, the anti-inflammatory activity of CHS-IVa may be via diminishing the phosphorylation of extracellular regulated protein kinases (ERK), p38, and c-Jun N-terminal kinase (JNK). Collectively, these findings will help to understand of the anti-inflammatory effects and mechanisms of P. japonicas deeply, and suggest a validated therapeutic use as an anti-inflammatory medication.

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Impressic Acid Attenuates the Lipopolysaccharide-Induced Inflammatory Response by Activating the AMPK/GSK3β/Nrf2 Axis in RAW264.7 Macrophages

International Journal of Molecular Sciences ◽

10.3390/ijms22020762 ◽

2021 ◽

Vol 22 (2) ◽

pp. 762

Author(s):

Gi Ho Lee ◽

Ji Yeon Kim ◽

Sun Woo Jin ◽

Thi Hoa Pham ◽

Jin Song Park ◽

...

Keyword(s):

Signaling Pathway ◽

Inflammatory Cytokines ◽

Molecular Mechanisms ◽

Inflammatory Diseases ◽

Raw264.7 Cells ◽

Raw264.7 Macrophages ◽

Nrf2 Signaling Pathway ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines ◽

Inflammatory Effect

Inflammatory diseases are caused by excessive inflammation from pro-inflammatory mediators and cytokines produced by macrophages. The Nrf2 signaling pathway protects against inflammatory diseases by inhibiting excessive inflammation via the regulation of antioxidant enzymes, including HO-1 and NQO1. We investigated the anti-inflammatory effect of impressic acid (IPA) isolated from Acanthopanax koreanum on the lipopolysaccharide (LPS)-induced inflammation and the underlying molecular mechanisms in RAW264.7 cells. IPA attenuated the LPS-induced production of pro-inflammatory cytokines and reactive oxygen species, and the activation of the NF-κB signaling pathway. IPA also increased the protein levels of Nrf2, HO-1, and NQO1 by phosphorylating CaMKKβ, AMPK, and GSK3β. Furthermore, ML385, an Nrf2 inhibitor, reversed the inhibitory effect of IPA on LPS-induced production of pro-inflammatory cytokines in RAW264.7 cells. Therefore, IPA exerts an anti-inflammatory effect via the AMPK/GSK3β/Nrf2 signaling pathway in macrophages. Taken together, the findings suggest that IPA has preventive potential for inflammation-related diseases.

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